The long-term objective of this project is to develop a laboratory test for monitoring low level toxicity from chemical exposure at levels which do not produce acute symptoms such as cytotoxicity, but which produce detectable damage later. The specific aims for the Phase I investigations are: (a) To determine the sub cytotoxic levels of three environmental agents,a mycotoxin, a polycyclic hydrocarbon and an aromatic amine. (b) Set a fairly long-term (3 to 4 months) bioassay using a well-characterized rat liver epithelial cell-line, exposed chronically to the above sub-cytotoxic doses of carcinogens. (c) Monitor the emergence of a population of cells containing mutated ras oncogene using molecular biological endpoints. The technical innovations in these studies include PCR amplification of low levels of chemically induced mutation in an oncogene from mammalian cells and their measurements and detections with liquid hybridization/gel retardation assay. The commercial application of this project is the screening of chemicals that exerts subtle alterations in the protooncogene by low level exposure that stimulates human exposure to environmental carcinogens.